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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An acute animal model with irreversible ischemia in the pons (Pons Ischemic Rat, PIR) was developed by two placed occlusions of the basilar artery. PIR showed decerebrate syndromes. Electroencephalograms (EEGs) in d-tubocurarine-immobilized PIR showed inclusion of obviously higher amplitude slower waves in the cortex but similar theta waves in the hippocampus, as compared with those in intact rats. Spontaneous cortical EEGs in PIR were desynchronized by pinching of hind limbs. From the frequency analysis, it was found that this cortical EEG alterations were composed of the decrease of beta 2 band relative power and the increase of delta-theta 2 bands. Haloperidol, at the dose without effect on EEG in intact rats, dose-relatedly decreased the cortical beta 2 band in PIR, and the potency was 100 times stronger than that in intact rats. On the other hand, the potency of atropine on the cortical beta 2 band was almost the same in both preparations. Apomorphine, thyrotropin-releasing hormone (TRH), methamphetamine, physostigmine and amantadine dose-relatedly increased the cortical beta 2 band in PIR, and these increasing effects, except in the case of physostigmine, were antagonized by the pretreatment of haloperidol. These results suggest that PIR is positioned as an animal model with the moderately lowered consciousness level intensively corresponding to semi coma in patients, and the dopaminergic system plays an important role rather than the cholinergic system in PIR.
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PMID:Acute EEG changes in rats by brainstem ischemia and its dopaminergic involvement. 286 70

Oxidative stress is thought to be the cause of nerve cell death in many CNS pathologies, including ischemia, trauma, and neurodegenerative disease. Glutamate kills nerve cells that lack ionotropic glutamate receptors via the inhibition of the cystine-glutamate antiporter x(c)(-), resulting in the inhibition of cystine uptake, the loss of glutathione, and the initiation of an oxidative stress cell death pathway. A number of catecholamines were found to block this pathway. Specifically, dopamine and related ligands inhibit glutamate-induced cell death in both clonal nerve cell lines and rat cortical neurons. The protective effects of dopamine, apomorphine, and apocodeine, but not epinephrine and norepinephrine, are antagonized by dopamine D4 antagonists. A dopamine D4 agonist also protects, and this protective effect is inhibited by U101958, a dopamine D4 antagonist. Although the protective effects of some of the catecholamines are correlated with their antioxidant activities, there is no correlation between the protective and antioxidant activities of several other ligands. Normally, glutamate causes an increase in reactive oxygen species (ROS) and intracellular Ca(2+). Apomorphine partially inhibits glutamate-induced ROS production and blocks the opening of cGMP-operated Ca(2+) channels that lead to Ca(2+) elevation in the late part of the cell death pathway. These data suggest that the protective effects of apomorphine on oxidative stress-induced cell death are, at least in part, mediated by dopamine D4 receptors via the regulation of cGMP-operated Ca(2+) channels.
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PMID:The activation of dopamine D4 receptors inhibits oxidative stress-induced nerve cell death. 1148 30

Apomorphine is a potent antioxidant that infiltrates through biological membranes. We studied the effect of apomorphine (2 microM) on myocardial ischemic-reperfusion injury in the isolated rat heart. Since iron and copper ions (mediators in formation of oxygen-derived free radicals) are released during myocardial reperfusion, apomorphine interaction with iron and copper and its ability to prevent copper-induced ascorbate oxidation were studied. Apomorphine perfused before ischemia or at the commencement of reperfusion demonstrated enhanced restoration of hemodynamic function (i.e. recovery of the work index (LVDP x HR) was 69.2 +/- 4.0% with apomorphine pre-ischemic regimen vs. 43.4 +/- 9.01% in control hearts, p < 0.01, and 76.3 +/- 8.0% with apomorphine reperfusion regimen vs. 30.4 +/- 11.1% in controls, p < 0.001). This was accompanied by decreased release of proteins in the effluent and improved coronary flow recovery in hearts treated with apomorphine after the ischemia. Apomorphine forms stable complexes with copper and with iron, and inhibits the copper-induced ascorbate oxidation. It is suggested that these iron and copper chelating properties and the redox-inactive chelates formed by transition metals and apomorphine play an essential role in post-ischemic cardioprotection.
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PMID:Cardioprotective and antioxidant effects of apomorphine. 1291 Dec 68

This study examined the hypothesis that low-concentration apomorphine improves postischemic hemodynamic and mitochondrial function in the isolated rat heart model by attenuating oxidation of myocardial proteins. Control and apomorphine-treated hearts were subjected to 35 min of perfusion, 25 min of normothermic global ischemia, and 60 min of reperfusion. Apomorphine (2 microM) was introduced into the perfusate for 20 min starting from the onset of reperfusion. Apomorphine significantly (p <.05) improved postischemic hemodynamic function: work index of the heart (product of LVDP and heart rate) was twice as high in apomorphine-treated hearts compared to controls at the end of reperfusion (p <.01). After isolation of cardiac mitochondria, the respiratory control ratio (RCR) was calculated from the oxygen consumption rate of State 3 and State 4 respiration. Apomorphine significantly improved postischemic RCR (87% of preischemic value vs. 39% in control, p <.05). Using an immunoblot technique, carbonyl content of multiple unidentified myocardial proteins (mitochondrial and nonmitochondrial) was observed to be elevated after global ischemia and reperfusion. Apomorphine significantly attenuated the increased protein oxidation at the end of reperfusion. These results support the conclusion that apomorphine is capable of preventing ischemia/reperfusion-induced oxidative stress and thereby attenuating myocardial protein oxidation and preserving mitochondrial respiration function.
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PMID:Apomorphine prevents myocardial ischemia/reperfusion-induced oxidative stress in the rat heart. 1533 13

Apomorphine (Apo), a dopaminergic agonist used for treatment of Parkinson disease, is a potent antioxidant. In addition to its antioxidative effects, the dopaminergic and adrenergic effects of Apo were studied. Isolated perfused rat hearts were exposed to 25 min of no-flow global ischemia (37 degrees C) and 60 min of reperfusion (I/R, control). Drugs were introduced for the first 20 min of reperfusion. The LVDP of the control group recovered to 54.6 +/- 3.3%. Apo-treated hearts had significantly improved recovery (61.6 +/- 5%, p < 0.05). The recovery of the work index LVDP x HR was even bigger: 67.8 +/- 3.7% (Apo treatment) vs 41.7 +/- 4.6% (control, p < 0.001). Haloperidol, a dopaminergic antagonist, did not affect the recovery with Apo. Propranolol, a beta-adrenergic blocker, initially inhibited the effect of Apo. However, the recovery of the combined group (Apo + propranolol) increased and reached significance (LVDP, p < 0.05 vs control group) after cessation of propranolol perfusion. At 60 min of reperfusion this group was superior to Apo-treated hearts (LVDP, p < 0.05). Propranolol (without Apo) did not improve the hemodynamic recovery. The same pattern of recovery applies also to the recovery of the +dP/dt during the reperfusion. L-DOPA was less effective than Apo. I/R caused significant increase in carbonylation of proteins. Apomorphine inhibited the increase in carbonylation. Haloperidol did not affect this beneficial effect of Apo. L-DOPA significantly decreased the carbonylation of proteins. We conclude that the antioxidative effect of Apo is its main mechanism of cardioprotection.
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PMID:Apomorphine-induced myocardial protection is due to antioxidant and not adrenergic/dopaminergic effects. 1667 10

Apomorphine was administered by continuous infusion in the mouse following acute inhibition of oxidative metabolism induced by systemic administration of MPTP, and in the gerbil following transient occlusion of the carotid arteries. The dosage employed was comparable to the one used in the treatment of severe on-off fluctuations in Parkinson's disease. The results show that apomorphine significantly diminishes the striatal lesion caused by MPTP and the size of the infarct associated with the transient global ischemia. These data suggest that apomorphine is neuroprotective, probably by means of an antioxidant effect, at doses that are clinically used. The finding may be relevant to brain ischemia as well to chronic neurodegeneration.
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PMID:Protection by apomorphine in two independent models of acute inhibition of oxidative metabolism in rodents. 1683 51

There is evidence that excessive zinc (Zn(2+)) release from presynaptic terminals following brain injuries such as ischemia and severe epileptic seizures induces neuronal cell death. Apomorphine (Apo), a dopamine receptor agonist, has been shown to have pleiotropic biological functions. In this study, we investigated whether Apo protects cultured cortical neurons from neurotoxicity provoked by excessive Zn(2+) exposure. Pretreatment with Apo dose- and time-dependently ameliorated Zn(2+) neurotoxicity. In addition, pretreatment with Apo prevented intracellular nicotinamide adenine dinucleotide (NAD(+)) and ATP depletion caused by Zn(2+) exposure. Dopamine receptor antagonists did not influence Apo protection against Zn(2+) neurotoxicity. Apo is shown to be autoxidized to produce oxidized products such as reactive oxygen species and quinones. N-Acetylcysteine, a thiol compound, partially reduced Apo protection. Entry of Zn(2+) into neurons is thought to be a critical step of Zn(2+) neurotoxicity. Interestingly, we found that pretreatment with Apo decreased elevation of intracellular Zn(2+) levels after Zn(2+) exposure and induced mRNA expression of the zinc transporter ZnT1, which transports intracellular Zn(2+) out of cells, and metallothionein. Taken together, these results suggest that the protective effects of Apo are regulated, at least in part, by its oxidized products, and preventing intracellular accumulation of Zn(2+) contributes to Apo protection against Zn(2+) neurotoxicity.
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PMID:Protective effects of apomorphine against zinc-induced neurotoxicity in cultured cortical neurons. 2354 93

The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.
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PMID:A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models. 2922 Aug 63